摘要
非酒精性脂肪型肝炎(NASH)已逐渐成为世界范围内慢性肝病的一大重要病因,患者数量不断上升的同时还面临着诊断难及尚无一线药物上市的困局。受市场驱使,过氧化物酶体增殖物受体(PPARs)多重激动剂类药物因预期对症将有较好疗效而被广泛研究,部分在研新药已进入临床阶段。其中,PPAR-双重激动剂为一大热门。本论文将基于多个文献报道的化合物的结构特征,通过计算机模拟辅助设计新颖的PPAR-双重激动剂分子,并通过多步温和、操作简便的反应完成该化合物的合成。
Facing the problems of the expanding patient group,diagnostic difficulties and the lack of first-line drugs,nonalcoholic steatohepatitis( NASH) has already become one of the most popular type of chronic liver disease world-wide. Being propelled by the potential market,many kinds of peroxisome proliferators-activated receptor( PPAR) agonists are under discovering because of their expected mechanism related efficacy in NASH. Some of them are now in clinical trials. Based on the pioneering work on PPARs agonists,we have designed a novel PPAR-agonist. The structure was evaluated via CADD model,which indicated its potential activity. A synthetic scheme of this molecule with good yields and mild reaction conditions was also designed.
